Peptidoglycan (PG), a macromolecule unique to bacterial cell walls, has long been known for its role in maintenance of bacterial integrity. More recently it has been recognized that, given the opportunity to interact with host cells, PG and soluble PG fragments appear to possess a propensity to augment host immune responses and inflammatory reactions. The potential for in vivo interaction between PG derived from Neisseria gonorrhoeae and host tissues appears to be particularly great. Of particular interest is that gonococci exhibit extensive turnover of PG during exponential growth and shed the soluble PG fragments into the medium, a very unusual characteristic among gram-negative bacteria. We are testing the hypothesis that soluble fragments of gonococcal PG contribute to the inflammatory response and to tissue damage associated with gonococcal infections, e.g., the arthritis syndrome of disseminated gonococcal infections. We are addressing this problem by (1) chemically characterizing gonococcal PG fragments that might gain direct assess to host cells in vivo, (2) examining the ability of PG fragments to initiate in vitro reactions associated with inflammation and tissue damage, and (3) correlating the presence of PG and anti-PG antibody with clinical forms of gonococcal infections. Our previous results have indicated that the PG fragments released by growing gonococci are very unusual in that they possess non-reducing, 1,6-anhydro-muramyl ends. In addition, we have found that various gonococcal PG derivatives do initiate in vitro reactions that are associated with inflammation, e.g., react with antibody in "normal" human sera and in hyperimmune rabbit sera, consume complement, and possess intrinsic toxicity for human fallopian tube organ cultures. Building on these data, the current proposal emphasizes (1) the possible role of the novel anhydro-muramyl-containing fragments (and other PG fragments) in influencing the consequences of gonococcal infections, (2) assessment of PG release by gonococci grown under various "physiologically-relevant" conditions, and (3) definition of the structural requirements of PG-mediated biological activities. We feel that the postulated role of PG in gonococcal infections might also operate in other destructive inflammatory conditions.